1. Field of the Invention
This invention relates to a macroencapsulated device for live cells. More particularly, it relates to materials and devices for transplantation and implantation of foreign cells and biological materials.
2. The Prior Art
Rapid advances in the field of biotechnology have lead to the development of novel biomaterials in which different types of somatic cells are encapsulated or combined with a variety of biopolymers in an attempt to restore, maintain, or improve tissue or organ function. The cell or biological component of the somatic cell-biomaterial combination secretes special chemicals or hormones while the biomaterial component protects the cells from immune attacks and at the same time is biocompatible with the host tissue. Tissue engineering approaches have microfabricated immunoprotective barriers around different types of somatic cells, namely neural, endocrine and hepatic cells. Immunoprotective barriers around donor islet cells as a therapeutic approach for the cure of diabetes is described as an example.
Islet cells have been encapsulated within alginate gel, with a technique called microencapsulation. U.S. Pat. No. 5,144,016 to Skjak-Braek et al discloses the chemistry, behavior and gelling properties of alginate material in different solutions. U.S. Pat. No. 4,352,883 to Lim discloses a method for encapsulating biological material such as living tissue, individual cells, hormones, enzymes or antibodies using Na alginate material. Microencapsulation of islet cells using alginate is disclosed in U.S. Pat. No. 4,391,909 to Lim. U.S. Pat. No. 5,459,054 to Skjak-Braek et al discloses encapsulation technology using purified Na alginate material with a high `G` polymer content. The `G` and `M` polymer content of alginate is discussed in U.S. Pat. No. 5,578,314 to Cochrum et al, U.S. Pat. No. 5,693,514 to Dorian et al, and Sun Y. et al, Normalization of Diabetes in Spontaneously Diabetic Cynomologus Monkeys by Xenografts of Microencapsulated Porcine Islets without Immunosuppression (J. Clin. Invest., Volume 98, No. 6, 1996, 1417-1422).
The technique of gel suspending large numbers of islet cells together, for example within hollow fibers, is referred to as macroencapsulation. The use of synthetic material such as PAN-PVC hollow fibers for the construction of an artificial pancreas is disclosed in U.S. Pat. No. 5,002,661 to Chick et al. Islet cells encapsulated within PAN-PVC fibers is also discussed in R. P. Lanza et al, Hollow Fibers and Macroencapsulation (Methods in Cell Transplantation, pgs. 611-615, Chapter G16, R. G. Landes, 1995). However, the use of commercial grade or low purity alginate in these devices causes fibroblast overgrowth which leads to loss of porosity and death of the encapsulated cells. One group described using agarose to suspend pig islets within long strands of polysulfone fibers having pores with 100, 30, and 10 kDa cutoffs in S. C. Cheung et al, Effect of Molecular weight Exclusion of Polysulfone Fibers on Macroencapsulated Pig Islet Xenograft Function in Diabetic Mice (16 Transplantation Proceedings, pgs. 2144-2145, Elsevier Science Inc., N.Y., 1997). The long strands were bent into circular coils and their ends were sealed with heated clamps which resulted in fibrous build-up after only about 40 days of implantation. Other approaches for end sealing are disclosed in U.S. Pat. No. 5,653,687 and U.S. Pat. No. 5,653,888, both to Mills et al.